Etiology and evaluation of chronic constipation in adults

INTRODUCTION — Constipation is the most common digestive complaint in the general population and is associated with substantial economic costs [1-3]. Symptoms of constipation include hard stools, excessive straining, infrequent bowel movements (<3 per week), a sense of incomplete evacuation, or the use of manual maneuvers to facilitate defecation. Symptoms which last >3 months are considered chronic.

The etiology, and evaluation of chronic constipation will be reviewed here. The management of chronic constipation is discussed separately. The recommendations in this topic are largely consistent with guidelines from the American Gastroenterological Association (AGA) and American Society for Gastrointestinal Endoscopy [4,5]. (See "Management of chronic constipation in adults".)

EPIDEMIOLOGY — Estimates of the prevalence of chronic constipation in North America have ranged from 12 to 19 percent [6,7]. Self-reported constipation appears to be more prevalent in females and those over age 60. It is more prevalent in individuals with little daily physical activity, lower income, and poor education [8]. In a meta-analysis of 26 studies, the pooled prevalence of chronic constipation in females was almost twofold that in males (17.4 versus 9.2 percent, OR 2.2, 95% CI 1.87-2.62) [7].

The prevalence of chronic constipation increases with age, most dramatically in patients 65 years of age or older [6,9,10]. In this age group, approximately 26 percent of males and 34 percent of females have symptoms of constipation [10,11]. Constipation appears to correlate with decreased caloric intake in older adults but not with either fluid or fiber intake [8,12,13]. (See "Constipation in the older adult", section on 'Epidemiology and risk factors'.)

In one study of 277 patients with chronic symptoms of constipation, 71 percent were due to irritable bowel syndrome [14]. Dyssynergic defecation, slow transit constipation, or a combination of the two were responsible for 13, 11, and 5 percent, respectively. (See 'Chronic idiopathic constipation' below and 'Irritable bowel syndrome with constipation' below.)

ETIOLOGY AND PATHOGENESIS

Secondary chronic constipation

●Neurogenic disorders – Diseases of the central and peripheral nervous systems are often associated with constipation as colonic and anorectal motor functions are coordinated by enteric, sympathetic, and parasympathetic nerves [15]. The distal colon receives parasympathetic innervation from the sacral nerves that pass through the pelvis and enter the bowel wall in the rectum. Transection of these nerves or lesions in the cauda equina may produce constipation associated with hypomotility, colonic dilatation, decreased rectal tone and sensation, stasis of the distal colon, and impaired defecation. Similar findings may occur with injury to the lumbosacral spine, with a meningomyelocele, and following low spinal anesthesia. Constipation may also be a result of high spinal cord damage. However, in contrast to lower cord damage, colonic reflexes are intact, and defecation can often be triggered by digital stimulation of the anal canal. (See "Chronic complications of spinal cord injury and disease", section on 'Gastrointestinal complications'.)

The high prevalence of constipation in multiple sclerosis and Parkinson disease may be worsened by physical inactivity or the use of medications with constipating side effects [16]. Severely constipated patients with advanced multiple sclerosis appear to have absent colonic motor responses after eating a meal and other characteristic changes that may result from interruption of normal cortical inhibition of colonic motor activity [17].

Hirschsprung disease is a congenital disorder characterized by obstipation from birth and colonic dilatation proximal to a spastic, non-relaxing, and nonpropulsive segment of distal bowel. Functional obstruction of the distal bowel is due to absent intramural ganglion cells of the submucosal and myenteric plexuses, a result of arrest of the caudal migration of neural crest cells during embryonic development. One genetic defect identified in patients with this disorder is an inactivating mutation in the RET proto-oncogene; another is a mutation in the endothelin B receptor [18,19]. Interestingly, activating mutations in RET lead to multiple endocrine neoplasia type 2 and familial medullary thyroid cancer. (See "Classification and genetics of multiple endocrine neoplasia type 2" and "Diabetic autonomic neuropathy of the gastrointestinal tract" and "Anorexia nervosa in adults and adolescents: Medical complications and their management", section on 'Constipation'.)

●Non-neurogenic disorders – Constipation may occur secondary to metabolic disorders, obstructing lesions of the gastrointestinal tract, including colorectal cancer, endocrine disorders such as diabetes mellitus, and psychiatric disorders such as anorexia nervosa (table 1).

●Medications – Constipation may also be due to a side effect of medications (table 2).  

Chronic idiopathic constipation

Normal transit or functional constipation — The majority of patients with chronic idiopathic constipation have normal-transit constipation (also known as functional constipation or constipation without identifiable structural or biochemical cause).

An international working committee recommended diagnostic criteria (Rome IV) for functional constipation [20,21]. The diagnosis should be based upon the presence of the following for at least three months (with symptom onset at least six months prior to diagnosis).

●Must include two or more of the following:

•Straining during more than 25 percent of defecations.

•Lumpy or hard stools (Bristol Stool Scale Form 1 to 2) in more than 25 percent of defecations [22].

•Sensation of incomplete evacuation for more than 25 percent of defecations.

•Sensation of anorectal obstruction/blockage for more than 25 percent of defecations.

•Manual maneuvers to facilitate more than 25 percent of defecations (eg, digital evacuation, support of the pelvic floor).

•Fewer than three spontaneous bowel movements per week.

●Loose stools are rarely present without the use of laxatives.

●There are insufficient criteria for irritable bowel syndrome (IBS). (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)

Although patients with functional constipation may have abdominal pain and/or bloating, they are not the predominant symptoms.

Patients who complain of infrequent defecation and are unresponsive to laxatives and fiber supplements may have normal colonic transit [23]. Those with normal transit constipation may misperceive bowel frequency and often exhibit increased psychosocial distress [23,24]. Some of these patients demonstrate abnormalities of anorectal sensory and motor function that are indistinguishable from those in patients with slow transit constipation; the relationship of these findings to the patient's complaints is unclear.

Defecation disorder — Defecation normally involves the coordinated relaxation of the puborectalis and external anal sphincter muscles, together with increased intraabdominal pressure and inhibition of colonic segmenting activity. Defecation disorders result from the inability to coordinate the abdominal and pelvic floor muscles to evacuate stools. In adults, rectal evacuation disorders may be due to structural defects or functional in etiology (dyssynergic defecation or pelvic floor dyssynergia or functional outlet disorder) [25].  

The pathogenesis of dyssynergic defecation is not completely understood but is probably multifactorial. It is thought to be an acquired, learned dysfunction rather than an organic or neurogenic disease. In patients with dyssynergic defecation, ineffective defecation is associated with a failure to relax, or inappropriate contraction of, the puborectalis and external anal sphincter muscles (figure 1) [26]. This narrows the anorectal angle and increases the pressures of the anal canal so that evacuation is less effective. Relaxation of these muscles involves cortical inhibition of the spinal reflex during defecation; thus, this pattern may represent a conscious or unconscious act. (See "Fecal incontinence in adults: Etiology and evaluation", section on 'Physiology of defecation'.)

A diagnosis of dyssynergic defecation requires fulfilment of all the clinical criteria of functional constipation and the presence of abnormal findings on anorectal manometry and balloon expulsion. Manometric diagnostic criteria for dyssynergic defecation include inappropriate contraction of the pelvic floor or less than 20 percent relaxation of basal resting sphincter pressure with adequate propulsive forces during attempted defecation [27]. (See 'Anorectal manometry and balloon expulsion' below.)

Slow transit constipation — Patients with slow transit constipation have a resting colonic motility that is similar to normal controls but have little or no increase in motor activity after meals or with the administration of bisacodyl [28,29] and a blunted response to cholinergic agents [30].

These findings suggest dysfunction in the enteric nerve plexus. Decreased volume of interstitial cells of Cajal in the myenteric plexus have been demonstrated in resected colon specimens from some of these patients who have had colon resections [31]. These cells are believed to play an important role in governing colonic motility.

Irritable bowel syndrome with constipation — IBS is a functional disorder of brain-gut interaction characterized by the presence of recurrent abdominal pain associated with periods of constipation, diarrhea, or normal bowel function. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)

EVALUATION

History and physical examination — The initial evaluation of patients who present with chronic constipation should include a careful history and physical examination to identify secondary causes of constipation and alarm features that warrant additional evaluation for organic disease (algorithm 1). (See 'Secondary chronic constipation' above.)

●Assess for alarm features – Alarm features include the following:

•Hematochezia or heme-positive stool

•Iron deficiency anemia

•Weight loss of ≥10 pounds

•New onset of unexplained constipation

•Obstructive symptoms

•Family history of colon cancer or inflammatory bowel disease

●Character of symptoms – Duration of symptoms, the frequency and characteristics of the stool, and associated symptoms. This may be aided by obtaining a two-week diary of symptoms [24]. The Bristol Stool Scale Form should be used to record stool consistency.

The presence of recurrent abdominal pain associated with periods of constipation, diarrhea, or normal bowel function is suggestive of irritable bowel syndrome. The evaluation of patients with irritable bowel syndrome is disused in detail separately. (See "Clinical manifestations and diagnosis of irritable bowel syndrome in adults", section on 'Overview of diagnostic approach'.)

●Medical history – Many systemic or neurologic disorders that impair colonic motility affect organs outside of the gastrointestinal tract (table 1). Patients with these disorders may have other symptoms in addition to constipation.

●Medication use – The history should include exposure to medications that can cause constipation and the temporal relationship between starting a particular drug and the onset of constipation (table 2).

●Family history – Assessment should include the presence of inflammatory bowel disease, colorectal cancer, and celiac disease.

The abdominal examination is usually normal in patients with chronic constipation. A digital rectal examination can assess anal pressure at rest, when patients squeeze their anal sphincter and pelvic floor muscles, and during a simulated evacuation. Evacuation is normally accompanied by relaxation of the anal sphincter and puborectalis muscle and descent of the perineum by 1 to 4 cm. Patients with dyssynergic defecation may have high anal resting pressure (anismus), reduced or excessive perineal descent, and/or rectal prolapse. The puborectalis may not relax normally or paradoxically may contract during simulated evacuation (table 3) [32]. A normal rectal examination with no clinical evidence of dyssynergia practically excludes dyssynergic defecation, but positive signs of dyssynergia on rectal examination require confirmation on objective anorectal manometry testing [33,34]. (See 'Anorectal manometry and balloon expulsion' below.)

Laboratory tests — Laboratory tests in patients with constipation to evaluate for secondary organic causes that warrant additional evaluation include a complete blood cell count to identify anemia, serum glucose (for diabetes mellitus), calcium (for hypercalcemia), and thyroid-stimulating hormone (for hypothyroidism).

Patients with alarm features or age ≥45 years

Alarm features include the following (algorithm 1):

●Hematochezia or heme-positive stool

●Iron deficiency anemia

●Clinically significant weight loss (>5 percent of usual body weight over 6 to 12 months)

●New onset of unexplained constipation

●Obstructive symptoms

●Family history of colorectal cancer or inflammatory bowel disease

Endoscopy — We perform a colonoscopy in patients with alarm features and in patients aged ≥45 years presenting with constipation who have not previously had a colonoscopy. A diagnosis of chronic idiopathic constipation should be considered only after these other diseases have been excluded. (See 'Normal transit or functional constipation' above.)

Additional evaluation and management — Additional evaluation may be required based on symptoms (eg, abdominal computed tomography [CT] in a patient with abdominal pain and weight loss) or examination findings (eg, high-resolution anorectal manometry and balloon expulsion test if dyssynergic defecation is suspected based on digital rectal examination).

Plain films of the abdomen can detect significant stool retention in the colon and can monitor bowel cleansing in patients with fecal retention. However, a diagnosis of constipation should not be made based on a radiograph alone. Only a small percentage of patients with slow transit constipation have megacolon or megarectum. Megacolon and megarectum can occur together or separately. Although radiographic criteria exist to diagnose these entities, radiologic assessment does not always correlate with manometric evaluation [35,36].

Most patients with a normal colonoscopy and routine laboratory tests have chronic idiopathic constipation and can be managed as patients without alarm features. (See 'Therapeutic trial of fiber and laxatives' below.)

Patients without alarm features and age <45 years

Therapeutic trial of fiber and laxatives — Management of chronic constipation includes patient education, behavior modification, dietary changes, and osmotic or stimulant laxatives (algorithm 1). The management of constipation is discussed in detail, separately. (See "Management of chronic constipation in adults", section on 'General approach'.)

Patients with persistent symptoms — Patients with persistent symptoms despite a trial of fiber and laxatives should undergo additional evaluation (algorithm 1) [37].

Assessment for a defecation disorder

Anorectal manometry and balloon expulsion — Anorectal manometry (ARM) provides comprehensive information regarding the anal sphincter function at rest and during defecatory maneuvers as well as reflex activation of the pelvic floor [36,38,39]. The parameters that can be measured using ARM are rectal sensation and compliance, reflexive relaxation of the internal anal sphincter, and manometric patterns produced upon attempted expulsion of simulated stool (pseudodefecation) performed as part of the balloon expulsion test (BET) [40,41]. ARM with BET therefore helps with the diagnosis of dyssynergic defecation, rectal sensory problems, and the assessment of response to biofeedback therapy for treatment of dyssynergic defecation [42]. (See "Overview of gastrointestinal motility testing".)

●Technique – High resolution manometry (HRM) uses 12 circumferential sensors spaced at 1 cm intervals (figure 1) [43]. This provides greater physiologic resolution and minimizes motion artifact. A high-definition 3D anorectal manometry system using 256 circumferential transducers can be used to define anal pressure profiles with greater precision [44]. There is no evidence that HRM is superior to conventional manometry for clinical purposes. Moreover, studies with HRM indicate that many nonconstipated individuals have patterns similar to those of constipated patients with dyssynergia; this brings into question the specificity of manometric patterns thought to be abnormal [45]. Pressures recorded by the rectal balloon provide some indication of intraabdominal pressures generated during expulsion efforts, while pressure recordings of the anal sphincter transducers indicate relaxation or inappropriate contraction of the external anal sphincter. Manometry can identify abnormal sphincter responses during attempted expulsion of the manometer [26].

The BET is performed in conjunction with an ARM. However, the methodology for the BET has not been standardized. In most centers, the time required to evacuate a balloon filled with warm tap water, typically 50 mL, in the seated position is assessed.

●Interpretation – The characteristic normal pattern during expulsion of the manometer is an increase in intrarectal pressure and decrease in external sphincter pressure. In patients with dyssynergic defecation, there is an increase in external sphincter pressure during attempted expulsion of the manometer (figure 1). Manometric demonstration that the internal anal sphincter relaxes following rectal distension excludes Hirschsprung disease from diagnostic consideration.

For the BET, at most centers, the upper limit of normal is one minute [46]. In one study, results of the BET were evaluated in 286 consecutive patients with chronic constipation and 40 healthy controls. In this study, the balloon was expelled by 37 (93 percent) healthy controls within one minute and all controls in less than two minutes [47]. Among patients with constipation, 148 (52 percent) passed the balloon within five minutes (110 passed the balloon in 1 minute, 35 passed it in 1 to 2 minutes, and 3 passed it in 2 to 5 minutes). On repeat testing after 30 days of conservative treatment for constipation, the test results were reproducible in 280 (98 percent) patients with constipation, when a time of greater than two minutes was considered abnormal.

Defecography

●Indication – Defecography is indicated when results of an ARM and BET are inconclusive for a defecatory disorder [48]. Defecography is a fluoroscopic imaging study that provides information about anatomic (eg, rectocele, enterocele, and intussusception) and functional (dyssynergic defecation) disorders of the anorectum.

●Technique – Defecography is performed by placing approximately 150 mL of thickened barium into the patient's rectum and having the patient squeeze, cough, and bear down. Evacuation of the barium can be monitored by fluoroscopy while the patient sits on a specially constructed commode.

●Interpretation – Assessment of the anorectal structures and the anorectal angle is made at rest and during expulsion of the barium mixture. Dyssynergic defecation is diagnosed by the presence of insufficient descent of the perineum (<1 cm) and less than a normal change in the anorectal angle (<15 degrees).

Magnetic resonance (MR) and dynamic MR defecography can evaluate global pelvic floor anatomy and sphincter morphology and assess dynamic motion, thereby providing valuable information without ionizing radiation. However, some studies have reported a high rate of nondiagnostic studies in patients undergoing MR defecography due to deficient straining and evacuation [49,50]. In addition, MR defecography is not widely available.

Assessment of colonic transit — Patients with persistent constipation who do not have evidence of a defecation disorder should undergo further testing to identify slow colonic transit (algorithm 1). (See "Management of chronic constipation in adults", section on 'Pharmacologic therapy'.)

●Radiopaque marker study – The radiopaque marker study is commonly performed by measuring movement of radiopaque markers through the gut. Several different approaches have been used including single or multiple marker ingestion. The patient ingests a high fiber diet (20 to 30 g per day) while abstaining from laxatives, enemas, and medications that may affect bowel function for two to three days prior to the test. Radiopaque markers are swallowed, and their passage through the colon is monitored by abdominal radiographs. Markers are counted in the right, left, and rectosigmoid colons (defined by certain anatomical landmarks) and are followed as they move distally until expelled [38]. For routine clinical purposes, a single capsule with 24 markers is administered on day 1 and followed by single radiograph on day 6 (after 120 hours) (image 1). Colonic transit time (CTT) is defined as the time it takes for stool (feces) to pass through the colon.

Patterns of radiopaque marker movement may be used to identify the underlying etiology:

•Defecatory disorder – Markers progress normally through the proximal colon but stagnate in the rectum in those with outlet delay [25,51-53].

•Slow transit constipation – In patients with slow transit constipation, transit in the right colon or left colon is delayed. Retention of more than five markers on day 6 is considered abnormal and indicative of slow transit constipation. However, as patients with a defecatory disorder may also retain markers, a diagnosis of slow transit constipation should only be made after excluding a defecatory disorder.

●Scintigraphy – Scintigraphy uses a gamma-camera to assess the passage of a radioisotope (111In or 99Tc), administered either in a coated capsule that dissolves in the colon or terminal ileum or a non-digestible capsule administered with a test meal. The results are a weighted distribution of the radioisotope in the colon at 24 hours and, if necessary, at 48 hours. In patients with dyssynergic defecation, there is delayed overall colonic transit at 48 hours and ascending colon half emptying time. Regional scintigraphic transit profiles do not adequately differentiate dyssynergic defecation from slow transit constipation [54]. Both radiopaque markers and scintigraphy provide a quantitative assessment of colonic transit and are considered equivalent [55,56]. However, scintigraphy is not as widely available.

●Wireless motility capsule – The wireless motility capsule (WMC) can assess regional (gastric emptying, small bowel transit) and CTT and whole gut transit times (WGTT). The sensitivity and specificity are similar with those of radiopaque marker tests and scintigraphic gastric emptying [57]. The WMC has been validated against the radiopaque marker test in patients with chronic constipation [58,59]. WMC is well tolerated, has good compliance, and avoids the risks of radiation exposure. However, it is more expensive than the radiopaque marker study, and it is not clear that it provides added clinical value in most patients. It is no longer available in the United States.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Constipation".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Constipation in adults (The Basics)")

●Beyond the Basics topics (see "Patient education: Constipation in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Prevalence – The prevalence of chronic constipation ranges from 12 to 19 percent with a higher prevalence in females. The prevalence of chronic constipation increases with age, most dramatically in patients 65 years of age or older. (See 'Epidemiology' above.)

●Etiology – Constipation may occur secondary to metabolic disorders, obstructing lesions of the gastrointestinal tract, endocrine disorders, neurologic disorders, or medications. Chronic idiopathic constipation may result from a defecation disorder characterized by an inability to coordinate the abdominal and pelvic floor muscles, slow colonic transit, or may be functional without identifiable structural or biochemical cause. Patients with irritable bowel syndrome (IBS) may also present with constipation. IBS is characterized by the presence of recurrent abdominal pain associated with periods of constipation, diarrhea, or normal bowel function.

●Evaluation – The initial evaluation of patients who present with chronic constipation should include a history and physical examination and laboratory studies to identify secondary causes of constipation and alarm features that warrant additional evaluation for organic disease (algorithm 1). (See 'Secondary chronic constipation' above.)

Alarm features include the following:

•Hematochezia or heme-positive stool

•Iron deficiency anemia

•Clinically significant weight loss (>5 percent of usual body weight over 6 to 12 months)

•New onset of unexplained constipation

•Obstructive symptoms

•Family history of colorectal cancer or inflammatory bowel disease

●Patients with alarm features or age ≥45 years – We perform a colonoscopy in patients with alarm features and in patients aged ≥45 years with constipation who have not previously had a colonoscopy to exclude organic disease. Additional evaluation (eg, abdominal CT) may be required based on symptoms. (See 'Patients with alarm features or age ≥45 years' above.)

●Patients without alarm symptoms – Constipation in patients without alarm features can be managed with fiber and osmotic or stimulant laxatives. (See 'Therapeutic trial of fiber and laxatives' above.)

●Patients with persistent symptoms despite a trial of fiber and laxatives – Patients with persistent symptoms despite a trial of fiber and osmotic/stimulant laxatives should undergo evaluation for an underlying defecatory disorder with anorectal manometry with a balloon expulsion test. Defecography should be performed when results of anorectal manometry and rectal balloon expulsion are inconclusive for a defecatory disorder. Patients without evidence of a defecatory disorder should undergo an assessment of colonic transit to identify slow transit constipation. (See 'Patients with persistent symptoms' above.)